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CTCF is a barrier for 2C-like reprogramming

Author

Listed:
  • Teresa Olbrich

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

  • Maria Vega-Sendino

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

  • Desiree Tillo

    (Genetics Branch, CCR, NCI, NIH)

  • Wei Wu

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

  • Nicholas Zolnerowich

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

  • Raphael Pavani

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

  • Andy D. Tran

    (Laboratory of Cancer Biology and Genetics, CCR, NCI, NIH)

  • Catherine N. Domingo

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

  • Mariajose Franco

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

  • Marta Markiewicz-Potoczny

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

  • Gianluca Pegoraro

    (Laboratory of Receptor Biology and Gene Expression, CCR, NCI, NIH)

  • Peter C. FitzGerald

    (Genome Analysis Unit, CCR, NCI, NIH)

  • Michael J. Kruhlak

    (Laboratory of Cancer Biology and Genetics, CCR, NCI, NIH)

  • Eros Lazzerini-Denchi

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

  • Elphege P. Nora

    (University of California San Francisco
    University of California San Francisco)

  • André Nussenzweig

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

  • Sergio Ruiz

    (Laboratory of Genome Integrity, CCR, NCI, NIH)

Abstract

Totipotent cells have the ability to generate embryonic and extra-embryonic tissues. Interestingly, a rare population of cells with totipotent-like potential, known as 2 cell (2C)-like cells, has been identified within ESC cultures. They arise from ESC and display similar features to those found in the 2C embryo. However, the molecular determinants of 2C-like conversion have not been completely elucidated. Here, we show that the CCCTC-binding factor (CTCF) is a barrier for 2C-like reprogramming. Indeed, forced conversion to a 2C-like state by the transcription factor DUX is associated with DNA damage at a subset of CTCF binding sites. Depletion of CTCF in ESC efficiently promotes spontaneous and asynchronous conversion to a 2C-like state and is reversible upon restoration of CTCF levels. This phenotypic reprogramming is specific to pluripotent cells as neural progenitor cells do not show 2C-like conversion upon CTCF-depletion. Furthermore, we show that transcriptional activation of the ZSCAN4 cluster is necessary for successful 2C-like reprogramming. In summary, we reveal an unexpected relationship between CTCF and 2C-like reprogramming.

Suggested Citation

  • Teresa Olbrich & Maria Vega-Sendino & Desiree Tillo & Wei Wu & Nicholas Zolnerowich & Raphael Pavani & Andy D. Tran & Catherine N. Domingo & Mariajose Franco & Marta Markiewicz-Potoczny & Gianluca Peg, 2021. "CTCF is a barrier for 2C-like reprogramming," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25072-x
    DOI: 10.1038/s41467-021-25072-x
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    Cited by:

    1. Xiuxiao Tang & Pengguihang Zeng & Kezhi Liu & Li Qing & Yifei Sun & Xinyi Liu & Lizi Lu & Chao Wei & Jia Wang & Shaoshuai Jiang & Jun Sun & Wakam Chang & Haopeng Yu & Hebing Chen & Jiaguo Zhou & Cheng, 2024. "The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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